{"id":26887,"date":"2024-01-03T21:39:37","date_gmt":"2024-01-03T19:39:37","guid":{"rendered":"https:\/\/hho-bulgaria.com\/h2-gas-inhalation-improves-covid-19-severity\/"},"modified":"2024-01-29T21:27:30","modified_gmt":"2024-01-29T19:27:30","slug":"h2-gas-inhalation-improves-covid-19-severity","status":"publish","type":"post","link":"https:\/\/hho-bulgaria.com\/en\/h2-gas-inhalation-improves-covid-19-severity\/","title":{"rendered":"H2 gas inhalation improves COVID-19 severity"},"content":{"rendered":"<div class=\"jig-ncbiinpagenav\" data-jigconfig=\"smoothScroll: false, allHeadingLevels: ['h2'], headingExclude: ':hidden,.nomenu'\" id=\"ui-ncbiinpagenav-1\">\n<div class=\"fm-sec half_rhythm no_top_margin\">\n<div class=\"fm-flexbox\">\n<div class=\"fm-citation\">\n<div class=\"citation-default\">\n<div class=\"part1\"><span role=\"menubar\"><a href=\"#\" role=\"menuitem\" aria-expanded=\"false\" aria-haspopup=\"true\">J Thorac Dis.<\/a><\/span> 2020 Jun; 12(6): 3448\u20133452. <\/div>\n<div class=\"part2\">  <span class=\"doi\"><span>doi:&nbsp;<\/span><a href=\"\/\/doi.org\/10.21037%2Fjtd-2020-057\" target=\"_blank\" rel=\"noopener noreferrer\" ref=\"reftype=other&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CFront%20Matter&amp;TO=Content%20Provider%7CCrosslink%7CDOI\">10.21037\/jtd-2020-057<\/a><\/span><\/div>\n<\/div>\n<\/div>\n<div class=\"fm-ids\">\n<div class=\"fm-citation-pmcid\"><span class=\"fm-citation-ids-label\">PMCID: <\/span><span>PMC7330772<\/span><\/div>\n<div class=\"fm-citation-pmid\">PMID: <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32642277\">32642277<\/a><\/div>\n<\/div>\n<\/div>\n<h1 class=\"content-title\">Hydrogen\/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial<\/h1>\n<div class=\"half_rhythm\">\n<div class=\"contrib-group fm-author\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Guan%20WJ%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139814830268272\" co-class=\"co-affbox\">Wei-Jie Guan<\/a>,<sup><br \/>\n1<br \/>\n,<\/sup><sup><br \/>\n#<br \/>\n<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Wei%20CH%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139814830265888\" co-class=\"co-affbox\">Chun-Hua Wei<\/a>,<sup><br \/>\n2<br \/>\n,<\/sup><sup><br \/>\n3<br \/>\n,<\/sup><sup><br \/>\n#<br \/>\n<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Chen%20AL%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139814830261392\" co-class=\"co-affbox\">Ai-Lan Chen<\/a>,<sup><br \/>\n4<br \/>\n,<\/sup><sup><br \/>\n5<br \/>\n,<\/sup><sup><br \/>\n#<br \/>\n<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Sun%20XC%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139814830594416\" co-class=\"co-affbox\">Xiao-Cong Sun<\/a>,<sup><br \/>\n6<br \/>\n,<\/sup><sup><br \/>\n7<br \/>\n<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Guo%20GY%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139814830590928\" co-class=\"co-affbox\">Guang-Yun Guo<\/a>,<sup><br \/>\n8<br \/>\n<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Zou%20X%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139814830588560\" co-class=\"co-affbox\">Xu Zou<\/a>,<sup><br \/>\n9<br \/>\n,<\/sup><sup><br \/>\n10<br \/>\n<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Shi%20JD%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139814830585072\" co-class=\"co-affbox\">Jin-Dong Shi<\/a>,<sup><br \/>\n10<br \/>\n,<\/sup><sup><br \/>\n11<br \/>\n<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Lai%20PZ%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139814830581584\" co-class=\"co-affbox\">Pei-Zhen Lai<\/a>,<sup><br \/>\n12<br \/>\n<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Zheng%20ZG%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139814830579216\" co-class=\"co-affbox\">Ze-Guang Zheng<\/a>,<sup><br \/>\n1<br \/>\n<\/sup> and  <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Zhong%20NS%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139814830576848\" co-class=\"co-affbox\">Nan-Shan Zhong<\/a><sup><img decoding=\"async\" src=\"\/corehtml\/pmc\/pmcgifs\/corrauth.gif\" alt=\"corresponding author\"><\/sup><sup><br \/>\n1<br \/>\n<\/sup><\/div>\n<div style=\"display:none\" class=\"contrib-group aff-tip\">\n<div id=\"_co_idm139814830268272\">\n<h3 class=\"no_margin\">Wei-Jie Guan<\/h3>\n<p><sup>1<\/sup>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China;<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Guan%20WJ%5BAuthor%5D\">Wei-Jie Guan<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139814830265888\">\n<h3 class=\"no_margin\">Chun-Hua Wei<\/h3>\n<p><sup>2<\/sup>Department of Respiratory Medicine, Weifang Wei\u2019en Hospital, Weifang, China;<\/p>\n<p><sup>3<\/sup>Department of Respiratory Medicine, Wuhan Hanyang Hospital, Wuhan, China;<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Wei%20CH%5BAuthor%5D\">Chun-Hua Wei<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139814830261392\">\n<h3 class=\"no_margin\">Ai-Lan Chen<\/h3>\n<p><sup>4<\/sup>Department of Cardiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China;<\/p>\n<p><sup>5<\/sup>Department of Respiratory and Critical Care Medicine, Wuhan Hankou Hospital, Wuhan, China;<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Chen%20AL%5BAuthor%5D\">Ai-Lan Chen<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139814830594416\">\n<h3 class=\"no_margin\">Xiao-Cong Sun<\/h3>\n<p><sup>6<\/sup>Intensive Care Unit, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China;<\/p>\n<p><sup>7<\/sup>Intensive Care Unit, Shishou Hospital of Traditional Chinese Medicine, Shishou, China;<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Sun%20XC%5BAuthor%5D\">Xiao-Cong Sun<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139814830590928\">\n<h3 class=\"no_margin\">Guang-Yun Guo<\/h3>\n<p><sup>8<\/sup>Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China;<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Guo%20GY%5BAuthor%5D\">Guang-Yun Guo<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139814830588560\">\n<h3 class=\"no_margin\">Xu Zou<\/h3>\n<p><sup>9<\/sup>Department of Respiratory and Critical Care Medicine, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou, China;<\/p>\n<p><sup>10<\/sup>Department of Infectious Diseases, Leishenshan Hospital, Wuhan, China;<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Zou%20X%5BAuthor%5D\">Xu Zou<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139814830585072\">\n<h3 class=\"no_margin\">Jin-Dong Shi<\/h3>\n<p><sup>10<\/sup>Department of Infectious Diseases, Leishenshan Hospital, Wuhan, China;<\/p>\n<p><sup>11<\/sup>Department of Respiratory and Critical Care Medicine, Shanghai Fifth People\u2019s Hospital, Shanghai, China;<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Shi%20JD%5BAuthor%5D\">Jin-Dong Shi<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139814830581584\">\n<h3 class=\"no_margin\">Pei-Zhen Lai<\/h3>\n<p><sup>12<\/sup>Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Lai%20PZ%5BAuthor%5D\">Pei-Zhen Lai<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139814830579216\">\n<h3 class=\"no_margin\">Ze-Guang Zheng<\/h3>\n<p><sup>1<\/sup>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China;<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Zheng%20ZG%5BAuthor%5D\">Ze-Guang Zheng<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139814830576848\">\n<h3 class=\"no_margin\">Nan-Shan Zhong<\/h3>\n<p><sup>1<\/sup>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China;<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Zhong%20NS%5BAuthor%5D\">Nan-Shan Zhong<\/a><\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"half_rhythm\">\n<div class=\"togglers fm-copyright-license\"><a href=\"#\" class=\"pmctoggle\" rid=\"idm139814827512960_ai\">Author information<\/a> <a href=\"#\" class=\"pmctoggle\" rid=\"idm139814827512960_an\">Article notes<\/a> <a href=\"#\" class=\"pmctoggle\" rid=\"idm139814827512960_cpl\">Copyright and License information<\/a> <a href=\"\/pmc\/about\/disclaimer\/\" style=\"margin-left: 1em\">PMC Disclaimer<\/a><\/div>\n<div class=\"fm-authors-info hide half_rhythm\" id=\"idm139814827512960_ai\" style=\"display:none\">\n<div class=\"fm-affl\" id=\"aff1\"><sup>1<\/sup>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China;<\/div>\n<div class=\"fm-affl\" id=\"aff2\"><sup>2<\/sup>Department of Respiratory Medicine, Weifang Wei\u2019en Hospital, Weifang, China;<\/div>\n<div class=\"fm-affl\" id=\"aff3\"><sup>3<\/sup>Department of Respiratory Medicine, Wuhan Hanyang Hospital, Wuhan, China;<\/div>\n<div class=\"fm-affl\" id=\"aff4\"><sup>4<\/sup>Department of Cardiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China;<\/div>\n<div class=\"fm-affl\" id=\"aff5\"><sup>5<\/sup>Department of Respiratory and Critical Care Medicine, Wuhan Hankou Hospital, Wuhan, China;<\/div>\n<div class=\"fm-affl\" id=\"aff6\"><sup>6<\/sup>Intensive Care Unit, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China;<\/div>\n<div class=\"fm-affl\" id=\"aff7\"><sup>7<\/sup>Intensive Care Unit, Shishou Hospital of Traditional Chinese Medicine, Shishou, China;<\/div>\n<div class=\"fm-affl\" id=\"aff8\"><sup>8<\/sup>Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China;<\/div>\n<div class=\"fm-affl\" id=\"aff9\"><sup>9<\/sup>Department of Respiratory and Critical Care Medicine, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou, China;<\/div>\n<div class=\"fm-affl\" id=\"aff10\"><sup>10<\/sup>Department of Infectious Diseases, Leishenshan Hospital, Wuhan, China;<\/div>\n<div class=\"fm-affl\" id=\"aff11\"><sup>11<\/sup>Department of Respiratory and Critical Care Medicine, Shanghai Fifth People\u2019s Hospital, Shanghai, China;<\/div>\n<div class=\"fm-affl\" id=\"aff12\"><sup>12<\/sup>Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei<\/div>\n<div><sup><img decoding=\"async\" src=\"\/corehtml\/pmc\/pmcgifs\/corrauth.gif\" alt=\"corresponding author\"><\/sup>Corresponding author.<\/div>\n<div id=\"afn1\"><sup>#<\/sup>These authors contributed equally to this work.<\/div>\n<div id=\"cor1\"><em>Correspondence to:<\/em> Nan-Shan Zhong. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, China. Email: <a href=\"mailto:dev@null\" data-email=\"moc.361.piv@nahsnan\" class=\"oemail\">moc.361.piv@nahsnan<\/a>.<\/div>\n<\/div>\n<div class=\"fm-article-notes hide half_rhythm\" id=\"idm139814827512960_an\" style=\"display:none\">\n<div class=\"fm-pubdate half_rhythm\">Received 2020 May 20; Accepted 2020 Jun 15.<\/div>\n<\/div>\n<div class=\"permissions half_rhythm hide\" id=\"idm139814827512960_cpl\" style=\"display:none\">\n<div class=\"fm-copyright half_rhythm\"><a href=\"\/pmc\/about\/copyright\/\">Copyright<\/a> 2020 Journal of Thoracic Disease. All rights reserved.<\/div>\n<div class=\"license half_rhythm\"><em>Open Access Statement:<\/em> This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: <a href=\"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CFront%20Matter&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0<\/a>.<\/div>\n<\/div>\n<\/div>\n<div id=\"pmclinksbox\" class=\"links-box whole_rhythm\" role=\"complementary\" aria-label=\"Related or updated information about this article.\">\n<div><strong>This article has been corrected. <\/strong>See <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7475564\/\">J Thorac Dis. 2020 August; 12(8): 4591<\/a>.<\/div>\n<div style=\"border-top: 1px solid rgb(102, 102, 153); margin: 5px 19% 3px;\"><\/div>\n<\/div>\n<\/div>\n<div class=\"sec\"><\/div>\n<div id=\"ass-data\" class=\"tsec fm-sec whole_rhythm\" data-section=\"Featured_PMC_Datacitation\">\n<h2 class=\"nomenu\">Associated Data<\/h2>\n<dl data-count=\"2\" class=\"box-data-suppmats whole_rhythm no_bottom_margin\">\n<dt><a href=\"#\" rid=\"data-suppmats\" data-ga-action=\"click_feat_toggler\" data-ga-label=\"Supplementary Materials\" class=\"pmctoggle\">Supplementary Materials<\/a><\/dt>\n<dd id=\"data-suppmats\" style=\"display: none;\">\n<div class=\"half_rhythm\">\n<p>The article\u2019s supplementary files as<\/p>\n<\/div>\n<div class=\"half_rhythm\">\n<div><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7330772\/bin\/jtd-12-06-3448-coif.pdf\" data-ga-action=\"click_feat_suppl\">jtd-12-06-3448-coif.pdf<\/a><span style=\"color:gray\"> (1.0M)<\/span><\/div>\n<div class=\"small doi\"><span>DOI:&nbsp;<\/span>10.21037\/jtd-2020-057<\/div>\n<\/div>\n<\/dd>\n<\/dl>\n<\/div>\n<div id=\"sec-a.h.a\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><span role=\"menubar\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"menuitem\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/span><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec-a.h.atitle\">Introduction<\/h2>\n<p class=\"p p-first-last\">Coronavirus disease 2019 (COVID-19) has resulted in more than 8.7 million laboratory-confirmed cases and 0.46 million deaths globally (<a href=\"#r1\" rid=\"r1\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">1<\/a>). Few therapies, if any, have been shown to rapidly ameliorate the respiratory symptoms and prevent against the disease progression. An important mechanism contributing to dyspnea and disease progression in patients with COVID-19 might be the increased work of breathing because of the heightened airway resistance (<a href=\"#r2\" rid=\"r2\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">2<\/a>). Inhalation of hydrogen\/oxygen mixed gas (H<sub>2<\/sub>-O<sub>2<\/sub>) might have a role in the treatment of COVID-19 given the decreased resistance compared with room air when passing through the airways.<\/p>\n<\/div>\n<div id=\"sec-a.h.b\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec-a.h.btitle\">Methods<\/h2>\n<p class=\"p p-first\">Recently, we conducted an open-label multicenter clinical trial, between January 21<sup>st<\/sup> and March 23<sup>rd<\/sup>, 2020, among patients with laboratory-confirmed COVID-19 from seven hospitals in China. The patients were aged 18\u201385 years, and had dyspnea both on hospital admission and at enrollment [See Online Supplement (<a href=\"http:\/\/dx.doi.org\/10.21037\/jtd-2020-057\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">http:\/\/dx.doi.org\/10.21037\/jtd-2020-057<\/a>) for patient sources, inclusion\/exclusion criteria and outcome measures].<\/p>\n<p>Trial Registration: <a href=\"http:\/\/www.clinicaltrials.gov\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">www.clinicaltrials.gov<\/a>, No. <a id=\"__tag_1106098258\" class=\"tag_hotlink\" href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04378712\" ref=\"reftype=extlink-clinical-trial&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CResource%7CClinical%20Trials%7CClinicalTrials.gov\"><span class=\"tag-json\" style=\"display:none\">{&#8220;type&#8221;:&#8221;clinical-trial&#8221;,&#8221;attrs&#8221;:{&#8220;text&#8221;:&#8221;NCT04378712&#8243;,&#8221;term_id&#8221;:&#8221;NCT04378712&#8243;}}<\/span>NCT04378712<\/a>.<\/p>\n<p>Randomization was not applied because of the urgency to deal with the outbreak. Patients were assigned to treatment group and control group at the discretion of attending clinicians. On the basis of standard-of-care (<a href=\"#r3\" rid=\"r3\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">3<\/a>), patients in treatment group inhaled H<sub>2<\/sub>-O<sub>2<\/sub> (66% hydrogen; 33% oxygen) at 6 L\/min via nasal cannula by using the Hydrogen\/Oxygen Generator (model AMS-H-03, Shanghai Asclepius Meditec Co., Ltd., China) daily until discharge [see Figure E1 in Online Supplement (<a href=\"http:\/\/dx.doi.org\/10.21037\/jtd-2020-057\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">http:\/\/dx.doi.org\/10.21037\/jtd-2020-057<\/a>)]. Patients in control group received standard-of-care (with oxygen therapy each day) alone until discharge. Clinical assessments included the five-category ordinal scale [see Panel 1 in Online Supplement (<a href=\"http:\/\/dx.doi.org\/10.21037\/jtd-2020-057\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">http:\/\/dx.doi.org\/10.21037\/jtd-2020-057<\/a>)], four-category ordinary scale of dyspnea, coughing, chest distress and chest pain (0: None; 1: Mild; 2: Moderate; 3: Severe; 4: Very severe) and adverse events, performed on admission, at enrollment, at days 2 and 3, and the day before discharge (end-of-treatment). The primary endpoint was the proportion of patients with improved disease severity (by at least one scale). Secondary endpoints comprised the change from baseline in oxygen saturation and symptom scales.<\/p>\n<p class=\"p p-last\">Analyses of the full-analysis set were performed with R software version 3.5.1. Count (percentage) was adopted for summarizing categorical variables, and compared with Chi-square tests or Fisher\u2019s exact test. The relative risk (RR) along with the 95% confidence interval (95% CI) were calculated to reflect the likelihood of the event in treatment group. Continuous variables were presented with mean \u00b1 standard deviation, and compared with independent <em>t<\/em>-test or Wilcoxon rank-sum test. All testing was two-sided, with P&lt;0.05 being statistically significant.<\/p>\n<\/div>\n<div id=\"sec-a.h.c\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec-a.h.ctitle\">Results<\/h2>\n<p class=\"p p-first\">Of 633 patients being screened, 215 and 328 were excluded from treatment and control group [see Figure E2 in Online Supplement (<a href=\"http:\/\/dx.doi.org\/10.21037\/jtd-2020-057\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">http:\/\/dx.doi.org\/10.21037\/jtd-2020-057<\/a>)], respectively, because of the lack of dyspnea at enrollment. Finally, 44 patients were included in treatment group, and 46 in control group. The median duration of H<sub>2<\/sub>-O<sub>2<\/sub> and oxygen inhalation was 7.7 (interquartile range, 6.0\u201318.3) h and 24 (interquartile range, 22.6\u201324.0) h per day, respectively. The demographics and disease severity were comparable at baseline [see Table E1,E2 in Online Supplement (<a href=\"http:\/\/dx.doi.org\/10.21037\/jtd-2020-057\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">http:\/\/dx.doi.org\/10.21037\/jtd-2020-057<\/a>)].<\/p>\n<p>H<sub>2<\/sub>-O<sub>2<\/sub> inhalation resulted in significantly more patients with improved disease severity at day 2 (20.5% <em>vs.<\/em> 2.3%, P=0.019; RR: 9.0, 95% CI: 1.2\u201368.1) and 3 (31.8% <em>vs.<\/em> 11.5%, P=0.038; RR: 2.8, 95% CI: 1.1\u20137.1) and end-of-treatment (70.5% <em>vs.<\/em> 31.8%, P&lt;0.001; RR: 2.2, 95% CI: 1.4\u20133.6) (<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7330772\/figure\/f1\/\" target=\"figure\" class=\"fig-table-link figpopup\" rid-figpopup=\"f1\" rid-ob=\"ob-f1\" co-legend-rid=\"lgnd_f1\" rel=\"noopener\"><span><em>Figure 1<\/em><\/span><\/a>). The improvement of dyspnea scale (50.0% <em>vs.<\/em> 23.9%, P=0.019; RR: 2.1, 95% CI: 1.2\u20133.8) was greater in H<sub>2<\/sub>-O<sub>2<\/sub> treatment group at day 2. H<sub>2<\/sub>-O<sub>2<\/sub> inhalation improved chest distress and chest pain (all P&lt;0.05). The improvement in cough scale was greater in treatment group at days 2 and 3 (both P&lt;0.05). Furthermore, the improvement in resting oxygen saturation was greater after H<sub>2<\/sub>-O<sub>2<\/sub> inhalation (all P&lt;0.05, <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7330772\/table\/t1\/\" target=\"table\" class=\"fig-table-link figpopup\" rid-figpopup=\"t1\" rid-ob=\"ob-t1\" co-legend-rid=\"\" rel=\"noopener\"><span><em>Table 1<\/em><\/span><\/a>).<\/p>\n<p><!--fig ft0--><!--fig mode=article f1--><\/p>\n<div class=\"fig iconblock whole_rhythm\" id=\"f1\" co-legend-rid=\"lgnd_f1\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7330772\/figure\/f1\/\" target=\"figure\" rid-figpopup=\"f1\" rid-ob=\"ob-f1\" rel=\"noopener\"><!--fig\/graphic|fig\/alternatives\/graphic mode=\"anchored\" m1--><\/a><\/p>\n<div class=\"figure\" data-largeobj=\"\" data-largeobj-link-rid=\"largeobj_idm139814789446688\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7330772\/figure\/f1\/\" target=\"figure\" rid-figpopup=\"f1\" rid-ob=\"ob-f1\" rel=\"noopener\"><\/a><a class=\"inline_block ts_canvas\" href=\"\/core\/lw\/2.0\/html\/tileshop_pmc\/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&amp;p=PMC3&amp;id=7330772_jtd-12-06-3448-f1.jpg\" target=\"tileshopwindow\" rel=\"noopener\"><\/p>\n<div class=\"ts_bar small\" title=\"Click on image to zoom\"><\/div>\n<p><img decoding=\"async\" loading=\"lazy\" alt=\"An external file that holds a picture, illustration, etc.\nObject name is jtd-12-06-3448-f1.jpg\" title=\"Click on image to zoom\" class=\"tileshop\" src=\"https:\/\/hho-bulgaria.com\/wp-content\/uploads\/2024\/01\/jtd-12-06-3448-f1.jpg\"><\/a><\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm139814789446688\" style=\"display: none;\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7330772\/figure\/f1\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"icnblk_cntnt\" id=\"lgnd_f1\">\n<div><a class=\"figpopup\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7330772\/figure\/f1\/\" target=\"figure\" rid-figpopup=\"f1\" rid-ob=\"ob-f1\" rel=\"noopener\">Figure 1<\/a><\/div>\n<p><!--caption a7--><\/p>\n<div class=\"caption\">\n<p>Study design and the main treatment effects of H<sub>2<\/sub>-O<sub>2<\/sub> inhalation in patients with coronavirus disease 2019 who had dyspnea at enrollment. All endpoints but resting oxygen saturation were treated as categorical variables (improved <em>vs.<\/em> not improved) compared with the baseline levels. *, P&lt;0.05; **, P&lt;0.01. EOT, end-of-treatment, which was the day before hospital discharge.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<p><!--table ft1--><!--table-wrap mode=\"anchored\" t5--><\/p>\n<div class=\"table-wrap anchored whole_rhythm\" id=\"t1\">\n<h3>Table 1<\/h3>\n<p><!--caption a7--><\/p>\n<div class=\"caption\"><!--caption a8--><strong>Treatment effects in terms of the primary and secondary endpoints at different time points<\/strong><\/div>\n<div class=\"xtable\">\n<table frame=\"hsides\" rules=\"groups\" class=\"rendered small default_table\">\n<thead>\n<tr>\n<th rowspan=\"2\" valign=\"middle\" align=\"left\" scope=\"col\" style=\"border-bottom: solid 0.75pt\" colspan=\"1\">Variables<\/th>\n<th valign=\"middle\" colspan=\"5\" align=\"center\" scope=\"colgroup\" style=\"border-bottom: solid 0.75pt\" rowspan=\"1\">Day 2<\/th>\n<th rowspan=\"2\" valign=\"middle\" align=\"left\" scope=\"col\" style=\"border-bottom: solid 0.75pt\" colspan=\"1\"><\/th>\n<th valign=\"middle\" colspan=\"5\" align=\"center\" scope=\"colgroup\" style=\"border-bottom: solid 0.75pt\" rowspan=\"1\">Day 3<\/th>\n<th rowspan=\"2\" valign=\"middle\" align=\"left\" scope=\"col\" style=\"border-bottom: solid 0.75pt\" colspan=\"1\"><\/th>\n<th valign=\"middle\" colspan=\"5\" align=\"center\" scope=\"colgroup\" style=\"border-bottom: solid 0.75pt\" rowspan=\"1\">End-of-treatment<\/th>\n<\/tr>\n<tr>\n<th valign=\"middle\" colspan=\"1\" align=\"center\" scope=\"colgroup\" style=\"border-top: solid 0.75pt\" rowspan=\"1\">Treatment group<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">Control group<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">P value<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">RR<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">95%CI<\/th>\n<th valign=\"middle\" colspan=\"1\" align=\"center\" scope=\"colgroup\" style=\"border-top: solid 0.75pt\" rowspan=\"1\">Treatment group<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">Control group<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">P value<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">RR<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">95%CI<\/th>\n<th valign=\"middle\" colspan=\"1\" align=\"center\" scope=\"colgroup\" style=\"border-top: solid 0.75pt\" rowspan=\"1\">Treatment group<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">Control group<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">P value<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">RR<\/th>\n<th valign=\"middle\" align=\"center\" scope=\"col\" style=\"border-top: solid 0.75pt\" rowspan=\"1\" colspan=\"1\">95%CI<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">\n<em>n*<\/em>\n<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<\/tr>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">Patients with improvement in five-scale disease severity (%)<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">20.5<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">2.3<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.019<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">9<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(1.2, 68.1)<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">31.8<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">11.4<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.038<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">2.8<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(1.1, 7.1)<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">70.5<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">31.8<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">&lt;0.001<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">2.2<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(1.4, 3.6)<\/td>\n<\/tr>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">\n<em>n*<\/em>\n<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<\/tr>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">Patients with improvement in dyspnea scale (%)<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">50<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">23.9<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.019<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">2.1<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(1.2, 3.8)<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">70.5<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">56.5<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.249<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">1.2<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(0.9, 1.7)<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">93.1<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">91.3<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">&gt;0.999<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">1<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(0.9, 1.2)<\/td>\n<\/tr>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">\n<em>n*<\/em>\n<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">43<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">43<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">43<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<\/tr>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">Patients with improvement in chest distress scale (%)<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">51.2<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">23.9<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.015<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">2.1<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(1.2, 3.9)<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">76.7<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">47.8<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.01<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">1.6<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(1.1, 2.3)<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">81.4<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">63<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.063<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">1.3<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(1.0, 1.7)<\/td>\n<\/tr>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">\n<em>n*<\/em>\n<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<\/tr>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">Patients with improvement in chest pain scale (%)<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">40.9<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">&lt;0.001<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">NA<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">NA<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">45.5<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">2.2<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">&lt;0.001<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">20.9<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(2.9, 149.2)<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">54.6<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">6.5<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">&lt;0.001<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">8.4<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(2.7, 25.8)<\/td>\n<\/tr>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">\n<em>n*<\/em>\n<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">44<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">46<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<\/tr>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">Patients with improvement in cough scale (%)<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">45.5<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">13<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.002<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">3.5<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(1.5, 7.9)<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">59.1<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">30.4<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.012<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">1.9<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(1.2, 3.2)<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">79.6<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">60.9<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.089<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">1.3<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(1.0, 1.7)<\/td>\n<\/tr>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">\n<em>n*<\/em>\n<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">34<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">34<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">34<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">34<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">34<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">34<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<\/tr>\n<tr>\n<td valign=\"top\" align=\"left\" scope=\"row\" rowspan=\"1\" colspan=\"1\">Mean improvement in resting oxygen saturation** (%)<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">1.6<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.5<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.003<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(0.4, 1.8)<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">2.6<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.8<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">&lt;0.001<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(0.9, 2.7)<\/td>\n<td valign=\"top\" align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">4.1<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">2<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">0.001<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">\u2013<\/td>\n<td valign=\"top\" align=\"center\" rowspan=\"1\" colspan=\"1\">(0.9, 3.3)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm139814789444240\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7330772\/table\/t1\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"tblwrap-foot\">\n<p>Count (percentage) was adopted for summarizing categorical variables, and compared with Chi-square tests or Fisher\u2019s exact test. The relative risk (RR) and 95% confidence interval (95% CI) were calculated. Continuous variables were presented with mean \u00b1 standard deviation, and compared with independent <em>t<\/em>-test or Wilcoxon rank-sum test. The median duration of hydrogen inhalation was 64 h (interquartile range, 24\u2013175) h in treatment group, corresponding to 7.7 (interquartile range, 6.0\u201318.3) h per day. Oxygen therapy in control group lasted for a median of 24 (interquartile range, 22.6\u201324.0) h per day. *, denotes number of patients evaluated; **, mean difference at Day 2: 1.1; at Day 3: 1.8; at the End of the Treatment: 2.1. NA, not applicable.<\/p>\n<\/div>\n<\/div>\n<p>Similar findings were found when analyzing the outcome measures as the continuous variables [all P&lt;0.05, Table E3 in Online Supplement (<a href=\"http:\/\/dx.doi.org\/10.21037\/jtd-2020-057\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">http:\/\/dx.doi.org\/10.21037\/jtd-2020-057<\/a>)]. In the H<sub>2<\/sub>-O<sub>2<\/sub> treatment group, the dyspnea scale improved more significantly at end-of-treatment regardless of baseline disease severity [Table E4 in Online Supplement (<a href=\"http:\/\/dx.doi.org\/10.21037\/jtd-2020-057\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">http:\/\/dx.doi.org\/10.21037\/jtd-2020-057<\/a>)]. Patients who inhaled H<sub>2<\/sub>-O<sub>2<\/sub> for less than the median duration (64 h) still presented with consistently significant improvements [Table E5 in Online Supplement (<a href=\"http:\/\/dx.doi.org\/10.21037\/jtd-2020-057\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">http:\/\/dx.doi.org\/10.21037\/jtd-2020-057<\/a>)].<\/p>\n<p class=\"p p-last\">The most common adverse events were worsening of cough (6.8% in treatment group; 8.7% in control group) and chest distress (2.3% in treatment group; 21.7% in control group). Abnormal laboratory findings were rare (2.3% in treatment group; 13.0% in control group). No serious adverse events were reported [Table E6 in Online Supplement (<a href=\"http:\/\/dx.doi.org\/10.21037\/jtd-2020-057\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">http:\/\/dx.doi.org\/10.21037\/jtd-2020-057<\/a>)].<\/p>\n<\/div>\n<div id=\"sec-a.h.d\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec-a.h.dtitle\">Discussion<\/h2>\n<p class=\"p p-first\">This is the first multicenter randomized clinical trial that verifies the efficacy and safety of H<sub>2<\/sub>-O<sub>2<\/sub> inhalation in patients with COVID-19. The clinical benefits were likely to be attributable to the ability of H<sub>2<\/sub>-O<sub>2<\/sub> to decrease the inspiratory efforts due to the significantly lower resistance when passing through the respiratory tract compared with room air (previously verified with impulse oscillometry) (<a href=\"#r4\" rid=\"r4\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">4<\/a>). Patients with COVID-19 frequently presented with dyspnea, coughing, chest pain and distress, and oxygen desaturation (<a href=\"#r5\" rid=\"r5\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">5<\/a>), which cannot be rapidly ameliorated with other existing therapies (including oxygen therapy). The therapeutic effects of H<sub>2<\/sub>-O<sub>2<\/sub> became significant as early as days 2 and 3 and the amelioration of most respiratory symptoms persisted till the end-of-treatment, which again cannot be readily interpreted by miscellaneous supportive therapies including oxygen therapy.<\/p>\n<p>Heliox inhalation reportedly resulted in amelioration of dyspnea and decreased respiratory tract resistance in adults and children (<a href=\"#r6\" rid=\"r6\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">6<\/a>,<a href=\"#r7\" rid=\"r7\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">7<\/a>). However, due to the lower cost-effectiveness, heliox has not been recommended for routine clinical use. H<sub>2<\/sub>-O<sub>2<\/sub> could be generated via direct electrolysis of water using commercially available instrument which has made it possible for clinical application at home and in hospital settings (particularly in medical facilities critically lacking oxygen supplies). The safety profiles have rendered H<sub>2<\/sub>-O<sub>2<\/sub> inhalation particularly suitable for relieving dyspnea and other respiratory symptoms in patients with COVID-19, regardless of the disease severity.<\/p>\n<p class=\"p p-last\">Our study was limited by the open-label design and variable duration of H<sub>2<\/sub>-O<sub>2<\/sub> inhalation due to the urgency. We neither randomly assigned patients with COVID-19 due to the emergency nor matched the patients with propensity scores, which could have resulted in selection bias. The protocol for H<sub>2<\/sub>-O<sub>2<\/sub> inhalation was established empirically and might warrant optimization. Nonetheless, H<sub>2<\/sub>-O<sub>2<\/sub> inhalation might be considered useful to patients with dyspnea or those in facilities without sufficient oxygen supplies.<\/p>\n<\/div>\n<div id=\"sec-a.h.e\" class=\"tsec sec\"><a id=\"supplementary-material-sec\"><\/a><\/p>\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec-a.h.etitle\">Supplementary<\/h2>\n<p><!--\/article\/body\/sec\/--><\/p>\n<div class=\"sec suppmat\" id=\"supplementary-material-a.h.e.b\">\n<p>The article\u2019s supplementary files as<\/p>\n<\/div>\n<div class=\"sec suppmat\" id=\"su1\">\n<div class=\"sup-box half_rhythm\" id=\"d64e993\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7330772\/bin\/jtd-12-06-3448-coif.pdf\" data-ga-action=\"click_feat_suppl\">Click here to view.<\/a><sup>(1.0M, pdf)<\/sup><\/div>\n<\/div>\n<\/div>\n<div id=\"ack-a.i.a\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"ack-a.i.atitle\">Acknowledgement<\/h2>\n<div class=\"sec\">\n<p>We thank Drs. Chun-Liang Lei, Xiao-Dong Li for their participation in patient recruitment and Shanghai Asclepius Meditec Co., Ltd. for their provision of the Hydrogen\/Oxygen Generator (model AMS-H-03).<\/p>\n<p><em>Funding:<\/em> None.<\/p>\n<\/div>\n<\/div>\n<div id=\"notes-a.i.c\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"notes-a.i.ctitle\">Notes<\/h2>\n<p><em>Ethical Statement:<\/em> The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.<\/p>\n<\/div>\n<div id=\"fn-group-a.i.b\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"fn-group-a.i.btitle\">Footnotes<\/h2>\n<p><!--back\/fn-group--><\/p>\n<div class=\"fm-sec half_rhythm small\">\n<p class=\"fn sec\" id=\"fn1\">\n<p class=\"p p-first-last\"><em>Provenance and Peer Review:<\/em> Given the revisions and the wide concern and pressing importance of research relating to COVID-19, this short communication was managed via the rapid communication pathway and underwent internal review.<\/p>\n<\/p>\n<p class=\"fn sec\" id=\"fn-a.i.b.b\">\n<p class=\"p p-first-last\"><em>Conflicts of Interest:<\/em> All authors have completed the ICMJE uniform disclosure form (available at <a href=\"http:\/\/dx.doi.org\/10.21037\/jtd-2020-057\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">http:\/\/dx.doi.org\/10.21037\/jtd-2020-057<\/a>). Prof. Nanshan Zhong serves as the unpaid Editor-in-Chief of <em>Journal of Thoracic Disease<\/em>. Other authors have no conflicts of interest to declare.<\/p>\n<\/p>\n<\/div>\n<\/div>\n<div id=\"ref-list-a.i.d\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"ref-list-a.i.dtitle\">References<\/h2>\n<div class=\"ref-list-sec sec\" id=\"reference-list\">\n<div class=\"ref-cit-blk half_rhythm\" id=\"r1\">1. <span class=\"mixed-citation\">World Health Organization Coronavirus disease 2019 (COVID-19) Situation Reports. (accessed on June 22nd, 2020). 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Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med 2020. [Epub ahead of print]. <span class=\"nowrap\">[<a class=\"int-reflink\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7070509\/\">PMC free article<\/a>]<\/span> [<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32167524\" ref=\"reftype=pubmed&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CCitationRef&amp;TO=Entrez%7CPubMed%7CRecord\">PubMed<\/a>]<\/span><\/div>\n<div class=\"ref-cit-blk half_rhythm\" id=\"r6\">6. <span class=\"mixed-citation\">Morgan SE, Vukin K, Mosakowski S, et al.<br \/>\n<span class=\"ref-title\">Use of heliox delivered via high-flow nasal cannula to treat an infant with coronavirus-related respiratory infection and severe acute air-flow obstruction.<\/span><br \/>\n<span class=\"ref-journal\">Respir Care<\/span><br \/>\n2014;<span class=\"ref-vol\">59<\/span>:e166-70. 10.4187\/respcare.02728 [<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/25118308\" ref=\"reftype=pubmed&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CCitationRef&amp;TO=Entrez%7CPubMed%7CRecord\">PubMed<\/a>] [<a href=\"\/\/doi.org\/10.4187%2Frespcare.02728\" target=\"_blank\" rel=\"noopener noreferrer\" ref=\"reftype=other&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CCitationRef&amp;TO=Content%20Provider%7CCrosslink%7CDOI\">CrossRef<\/a>] <span class=\"nowrap\">[<a href=\"https:\/\/scholar.google.com\/scholar_lookup?journal=Respir+Care&amp;title=Use+of+heliox+delivered+via+high-flow+nasal+cannula+to+treat+an+infant+with+coronavirus-related+respiratory+infection+and+severe+acute+air-flow+obstruction.&amp;author=SE+Morgan&amp;author=K+Vukin&amp;author=S+Mosakowski&amp;volume=59&amp;publication_year=2014&amp;pages=e166-70&amp;pmid=25118308&amp;doi=10.4187\/respcare.02728&amp;\" target=\"_blank\" rel=\"noopener noreferrer\" ref=\"reftype=other&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CCitationRef&amp;TO=Content%20Provider%7CLink%7CGoogle%20Scholar\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Google Scholar<\/a>]<\/span><\/span><\/div>\n<div class=\"ref-cit-blk half_rhythm\" id=\"r7\">7. <span class=\"mixed-citation\">Kneyber MC, van Heerde M, Markhorst DG, et al.<br \/>\n<span class=\"ref-title\">Mechanical ventilation with heliox decreases respiratory system resistance and facilitates CO2 removal in obstructive airway disease.<\/span><br \/>\n<span class=\"ref-journal\">Intensive Care Med<\/span><br \/>\n2006;<span class=\"ref-vol\">32<\/span>:1676-7. 10.1007\/s00134-006-0348-6 [<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/16927073\" ref=\"reftype=pubmed&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CCitationRef&amp;TO=Entrez%7CPubMed%7CRecord\">PubMed<\/a>] [<a href=\"\/\/doi.org\/10.1007%2Fs00134-006-0348-6\" target=\"_blank\" rel=\"noopener noreferrer\" ref=\"reftype=other&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CCitationRef&amp;TO=Content%20Provider%7CCrosslink%7CDOI\">CrossRef<\/a>] <span class=\"nowrap\">[<a href=\"https:\/\/scholar.google.com\/scholar_lookup?journal=Intensive+Care+Med&amp;title=Mechanical+ventilation+with+heliox+decreases+respiratory+system+resistance+and+facilitates+CO2+removal+in+obstructive+airway+disease.&amp;author=MC+Kneyber&amp;author=M+van+Heerde&amp;author=DG+Markhorst&amp;volume=32&amp;publication_year=2006&amp;pages=1676-7&amp;pmid=16927073&amp;doi=10.1007\/s00134-006-0348-6&amp;\" target=\"_blank\" rel=\"noopener noreferrer\" ref=\"reftype=other&amp;article-id=7330772&amp;issue-id=360605&amp;journal-id=1685&amp;FROM=Article%7CCitationRef&amp;TO=Content%20Provider%7CLink%7CGoogle%20Scholar\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Google Scholar<\/a>]<\/span><\/span><\/div>\n<\/div>\n<\/div>\n<div style=\"display: none; width: 200px; top: -100px; left: -100px;\" aria-live=\"assertive\" aria-hidden=\"true\" class=\"ui-helper-reset ui-ncbipopper-wrapper ui-ncbilinksmenu\">\n<ul id=\"ui-ncbiinpagenav-2\">\n<li><a href=\"#sec-a.h.atitle\">Introduction<\/a><\/li>\n<li><a href=\"#sec-a.h.btitle\">Methods<\/a><\/li>\n<li><a href=\"#sec-a.h.ctitle\">Results<\/a><\/li>\n<li><a href=\"#sec-a.h.dtitle\">Discussion<\/a><\/li>\n<li><a href=\"#sec-a.h.etitle\">Supplementary<\/a><\/li>\n<li><a href=\"#ack-a.i.atitle\">Acknowledgement<\/a><\/li>\n<li><a href=\"#notes-a.i.ctitle\">Notes<\/a><\/li>\n<li><a href=\"#fn-group-a.i.btitle\">Footnotes<\/a><\/li>\n<li><a href=\"#ref-list-a.i.dtitle\">References<\/a><\/li>\n<\/ul>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Hydrogen\/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial<\/p>\n","protected":false},"author":1,"featured_media":17899,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[130],"tags":[],"disease":[853],"body-organ":[1027],"applications":[679],"test_subjects":[1519],"report-topic":[1370],"class_list":["post-26887","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-hydrogen-health","disease-sars-covid-2","body-organ-lung-2","applications-inhalation-2","test_subjects-human-2","report-topic-dyspnea-2"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>H2 gas inhalation improves COVID-19 severity<\/title>\n<meta name=\"description\" content=\"Hydrogen\/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent 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